This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is part of a large consortium on AIDS vaccine development sponsored by the Gates Foundation and the International AIDS Vaccine Initiative (IAVI). A major goal of the consortium is to develop new approaches to AIDS vaccine using the rhesus macaque model to assess efficacy and in particular compare efficacy of all approaches in an identical challenge protocol. The specific goal of this project is to design, construct and test gene-deleted RhCMV vectors that have been optimized for immunogenicity and safety, and then comparatively assess both wildtype RhCMV vectors and gene-deleted RhCMV vectors in the standard efficacy protocol developed for the entire consortium. RhCMV vectors will be tested alone as well as in heterologous prime-boost protocols using DNA and adenovirus vectors as the heterologous prime or boost. Work in the past year has confirmed the ability of RhCMV/SIV vectors to elicit SIV-specific effector memory T cell responses capable of providing early, high level protection against limiting does, intra-rectal SIVmac239 challenge. Currently work is investigating the duration of protection and the mechanisms responsible.